Systemic Inflammatory Response SyndromePhase 1/2THYTECH2NCT06052436
Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 and/or Acute Respiratory Distress Syndrome (THYTECH2)
A Phase 1/2 study testing Allogeneic thyTreg 5.000.000 and Allogeneic thyTreg 10.000.000 in people with Systemic Inflammatory Response Syndrome, run by Hospital General Universitario Gregorio Marañon at 1 site in Spain.
Trial summary
The investigators developed a GMP protocol to isolate Treg cells from thymic tissue (thyTreg). The thyTreg cells are being evaluated in a Phase I/II clinical trial to evaluate the safety and efficacy of the adoptive transfer of autologous thyTreg to prevent rejection in heart transplant children (NCT04924491), with… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Systemic Inflammatory Response Syndrome
- What is being tested?
- Allogeneic thyTreg 5.000.000 and Allogeneic thyTreg 10.000.000
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSpain
- Study dates
- 27 Jun 2023to 31 Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient over 18 to 65 years of age
- Patient Informed and non-opposed to the research by his medical doctor during hospitalization
- Patient with clinical, radiological, gasometric and immunological criteria defined as:
- Acute respiratory failure secondary to acute lung injury of noncardiogenic cause
- Pulmonary abnormalities compatible with bilateral alveoloinsterstitial infiltrates by chest imaging (radiograph or scan)
- PaO2/FiO2≤ 300 Presence of at least one of the following markers of inflammation: IL6 > 40 pg/ml or ferritin >300 ng/ml or CRP >3 mg/dl or increasing over the last 24 hours
Who cannot join
- Pregnancy or breast feeding
- Body mass index >35
- Patients not expected to survive 48 hours after enrolment based on clinical assessment
- Patients with an extracorporeal respiratory support
- Neutropenia (absolute neutrophil count <1000/uL)
- Thrombocytopenia (absolute neutrophil count <50000/uL)
Show all 17Show fewer
- Positive serology for HBV, HCV, or HIV at Screening
- Life expectancy of less than 6 months due to other pathologies
- History of significant underlying pulmonary disease requiring oxygen therapy prior to inclusion.
- Patients with a history of autoimmune diseases
- Patients with a history of hematopoietic neoplasia or oncology disease
- Patients with a history of hematopoietic or solid organ transplant
- Patients with a congenital or induced immunodeficiency
- Patients received thymoglobulin, basiliximab or any anti-T-cell therapies within 6 moths prior to the screening visit
- Patients received other cell therapy in the last 12 months
- Patients received intravenous immunoglobulin (IVIg) within 5 moths prior to the screening visit
- Patients who have participated or is participating in a clinical research study evaluating COVID-19 or ARDS within 30 days prior to the screening visit
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site, 1 recruiting
- Recruiting
Hospital General Universitario Gregorio Marañon
Madrid, Madrid, 28007
Rafael Correa-Rocha, PhD, +34 915866455, rafael.correa@iisgm.com
Marta Martínez-Bonet, PhD
About this study
Official title: Open Phase I/IIa Clinical Trial to Evaluate the Safety and Efficacy of Allogenic Administration of Treg Cells Obtained From Thymic Tissue (thyTreg) to Control The Immune Hyperactivation Associated With COVID-19 and/or Acute Respiratory Distress Syndrome
The investigators developed a GMP protocol to isolate Treg cells from thymic tissue (thyTreg). The thyTreg cells are being evaluated in a Phase I/II clinical trial to evaluate the safety and efficacy of the adoptive transfer of autologous thyTreg to prevent rejection in heart transplant children (NCT04924491), with preliminary results indicating the feasibility and safety of the therapy.
In addition, thyTreg cells have shown low immunogenicity in the pre-clinical setting, indicating that allogeneic use of these thyTreg cells (allo-thyTreg) would have a low risk of adverse effects. These thyTreg cells could inhibit an excessive inflammation in SARS-CoV-2 infection, or ameliorate the immunological affection underlying Acute respiratory distress syndrome, improving life-threatening manifestations, restoring immune balance, and protecting affected tissues.
This clinical trial is an open-label Sequential Parallel Group Phase I/II study to evaluate the safety and efficacy of allogeneic thymus derived Tregs (thyTreg) (thyTreg) in controlling the immune dysregulation associated with SARS-CoV-2 infection and/or Acute Respiratory Distress Syndrome.
Read the detailed description
The immune system is the body's defense system against pathogens and other harmful agents, but it is also responsible for transplant rejection or autoimmune diseases. Another scenario of disproportionate immune response is the Immune Hyperactivation, an exaggerated systemic inflammatory response such as that caused by respiratory infections like COVID-19, a major cause of acute respiratory distress syndrome (ARDS) in critically ill patients.
The standard treatment to prevent these immune responses is the use of immunosuppressive and immunomodulatory therapy, which produces a pleotropic inhibition on the immune system and have a high cost. However, a widespread feeling among the scientific community is that only re-educating immune system to promote immune tolerance will decline the harmful immune responses without prejudice to the functional integrity of the immune system.
In the context of severe COVID-19 and ARDS, it has been shown that an alteration in the frequency and functionality of Tregs. In addition, it has been described that the increased oxygen therapy requirements is not due to the viral effect, but to the triggered immune hyperinflammation that can lead to multi-organ failure and death. Therefore, although the adoptive transfer of Treg is a promising cell therapy for the treatment of this type of disease, the characteristics of the patients make it unfeasible to obtain enough Treg from the patient to produce a therapeutic dose and, if achieved, the quality of these cells does not allow a prolonged therapeutic effect to be obtained over time.
Tregs are a subset of CD4+ T cells with suppressive function that maintain the immune system balance. Adoptive Treg cell therapy has shown efficacy in a variety of immune-mediated diseases in preclinical and clinical studies. To date, most of the clinical trials employing Treg cell therapy have been limited due to a small Treg numbers obtained (Treg cells represent less than 10% of CD4+ T cells) and the low quality of infused Treg (in terms of purity, survival, and suppressor capacity).
The investigators have developed an innovative Treg manufacturing protocol, that overcome the existing difficulties by employing a new source of cells, which is the thymic tissue routinely removed and discarded in paediatric cardiac surgeries. The protocol allows to produce massive amounts of thymus derived Treg cells (thyTreg), with improved survival, high suppressive capacity and suitable for therapeutic use.
The study will evaluate escalating doses of thyTreg administrated as a single IV dose. The study will include up to 2 cohorts of 4 to 8 subjects per each arm (control group and thyTreg group) followed for a total of 24 months. All subjects will receive standard of care treatment for COVID-19 or ARDS, including dexamethasone and other approved therapies from institutional guidelines.
- Conditions
- Systemic Inflammatory Response Syndrome
- Being tested
- Allogeneic thyTreg 5.000.000, Allogeneic thyTreg 10.000.000
- Keywords
- Immune Hyperactivation, Regulatory T cell, ARDS, COVID-19, Advanced therapy, Immunotherapy, Th1-Th2 Balance
- Medical subject headings
- Systemic Inflammatory Response Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic thyTreg 5.000.000Biological
Also called Allogeneic thyTreg cells
Treg lymphocytic cells, differentiated, allogeneic, of thymic tissue, expanded and stimulated with Interleukin (IL-) 2 (thyTreg)
Allogeneic thyTreg 10.000.000Biological
Also called Allogeneic thyTreg cells
Treg lymphocytic cells, differentiated, allogeneic, of thymic tissue, expanded and stimulated with Interleukin (IL-) 2 (thyTreg)
| Study group | Role | What they receive |
|---|---|---|
| Phase A: 5.000.000 thyTreg /kg | Experimental | Allogeneic thyTreg 5.000.000 Receives: Biological: Allogeneic thyTreg 5.000.000 |
| Phase A: standard of care | No intervention | Standard of care |
| Phase B: 10.000.000 thyTreg /kg | Experimental | Allogeneic thyTreg 10.000.000 Receives: Biological: Allogeneic thyTreg 10.000.000 |
| Phase B: standard of care | No intervention | Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
1. Incidence of infusion-related adverse events (safety) by type, frequency, severity, and causality
Measured: 24 months
Secondary outcomes (16)
Length of intensive care unit stay
Measured: 24 months
Oxygenation improvement as assessed using PaO2/FiO2 and/or SaO2/FiO2
Measured: 24 months
Change in clinical status as assessed using Sequential Organ Failure Assessment Score
Measured: 24 months
Change in clinical status as assessed using Acute Physiology and Chronic Health disease Classification System (APACHE) III
Measured: 24 months
Change in clinical status as assessed using Barthel score
Measured: 24 months
Change in myocardial function as measured by mitral and tricuspid regurgitation using doppler echocardiography
Measured: 24 months
Change in myocardial function as measured by mitral and tissue mitral doppler using doppler echocardiography
Measured: 24 months
Change in myocardial function as measured by tricuspid and tissue tricuspid using doppler echocardiography
Measured: 24 months
Change in SARS-CoV-2 positivity or etiology of ARDS assessed using diagnostics test
Measured: 24 months
Change From Baseline in ferritin parameter
Measured: 24 months
Change From Baseline in interleukin 6 (IL-6)
Measured: 24 months
Change From Baseline in C-Reactive Protein (PCR)
Measured: 24 months
Change From Baseline in Treg cells number in peripheral blood
Measured: 24 months
Number of T cells, B cells, NK cells, monocytes, dendritic cells, and granulocytes in peripheral blood
Measured: 24 months
Change From Baseline in cytokines levels of interferon gamma, tumor necrosis factor alpha and interleukins (IL-6 and IL-10).
Measured: 24 months
Overall patient survival rate at 24 months
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2023
- Study start27 Jun 2023
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Inflammatory Response SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital General Universitario Gregorio Marañon
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto de Salud Carlos III
- Responsible party
- Principal investigator, Rafael Correa-Rocha, Hospital General Universitario Gregorio Marañon
- Investigators
- Rafael Correa-Rocha, PhD, Principal investigator, Hospital General Universitario Gregorio Marañon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06052436
- Sponsor's protocol ID
- FIBHGM-ECNC003-2021
- Other IDs
- 2024-519799-25, 2021-003240-25
- Acronym
- THYTECH2
- Status last verified
- Sep 2026
- First submitted
- 12 Sep 2023
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Phase I/IIa Clinical Trial to Evaluate the Safety and Efficacy of Allogenic Administration of Treg Cells Obtained From Thymic Tissue (thyTreg) to Control The Immune Hyperactivation Associated With COVID-19 and/or Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT06052436
- Acronym / sponsor ID
- THYTECH2 / FIBHGM-ECNC003-2021
- Conditions
- Systemic Inflammatory Response Syndrome
- Keywords
- Immune Hyperactivation, Regulatory T cell, ARDS, COVID-19, Advanced therapy, Immunotherapy, Th1-Th2 Balance
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Hospital General Universitario Gregorio MarañonUniversity, hospital or other
- Collaborators
- Instituto de Salud Carlos III
- Study start
- 27 Jun 2023 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 25 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators developed a GMP protocol to isolate Treg cells from thymic tissue (thyTreg). The thyTreg cells are being evaluated in a Phase I/II clinical trial to evaluate the safety and efficacy of the adoptive transfer of autologous thyTreg to prevent rejection in heart transplant children (NCT04924491), with preliminary results indicating the feasibility and safety of the therapy.
In addition, thyTreg cells have shown low immunogenicity in the pre-clinical setting, indicating that allogeneic use of these thyTreg cells (allo-thyTreg) would have a low risk of adverse effects. These thyTreg cells could inhibit an excessive inflammation in SARS-CoV-2 infection, or ameliorate the immunological affection underlying Acute respiratory distress syndrome, improving life-threatening manifestations, restoring immune balance, and protecting affected tissues.
This clinical trial is an open-label Sequential Parallel Group Phase I/II study to evaluate the safety and efficacy of allogeneic thymus derived Tregs (thyTreg) (thyTreg) in controlling the immune dysregulation associated with SARS-CoV-2 infection and/or Acute Respiratory Distress Syndrome.
Detailed description
The immune system is the body's defense system against pathogens and other harmful agents, but it is also responsible for transplant rejection or autoimmune diseases. Another scenario of disproportionate immune response is the Immune Hyperactivation, an exaggerated systemic inflammatory response such as that caused by respiratory infections like COVID-19, a major cause of acute respiratory distress syndrome (ARDS) in critically ill patients.
The standard treatment to prevent these immune responses is the use of immunosuppressive and immunomodulatory therapy, which produces a pleotropic inhibition on the immune system and have a high cost. However, a widespread feeling among the scientific community is that only re-educating immune system to promote immune tolerance will decline the harmful immune responses without prejudice to the functional integrity of the immune system.
In the context of severe COVID-19 and ARDS, it has been shown that an alteration in the frequency and functionality of Tregs. In addition, it has been described that the increased oxygen therapy requirements is not due to the viral effect, but to the triggered immune hyperinflammation that can lead to multi-organ failure and death. Therefore, although the adoptive transfer of Treg is a promising cell therapy for the treatment of this type of disease, the characteristics of the patients make it unfeasible to obtain enough Treg from the patient to produce a therapeutic dose and, if achieved, the quality of these cells does not allow a prolonged therapeutic effect to be obtained over time.
Tregs are a subset of CD4+ T cells with suppressive function that maintain the immune system balance. Adoptive Treg cell therapy has shown efficacy in a variety of immune-mediated diseases in preclinical and clinical studies. To date, most of the clinical trials employing Treg cell therapy have been limited due to a small Treg numbers obtained (Treg cells represent less than 10% of CD4+ T cells) and the low quality of infused Treg (in terms of purity, survival, and suppressor capacity).
The investigators have developed an innovative Treg manufacturing protocol, that overcome the existing difficulties by employing a new source of cells, which is the thymic tissue routinely removed and discarded in paediatric cardiac surgeries. The protocol allows to produce massive amounts of thymus derived Treg cells (thyTreg), with improved survival, high suppressive capacity and suitable for therapeutic use.
The study will evaluate escalating doses of thyTreg administrated as a single IV dose. The study will include up to 2 cohorts of 4 to 8 subjects per each arm (control group and thyTreg group) followed for a total of 24 months. All subjects will receive standard of care treatment for COVID-19 or ARDS, including dexamethasone and other approved therapies from institutional guidelines.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase A: 5.000.000 thyTreg /kg | Experimental | Biological: Allogeneic thyTreg 5.000.000Allogeneic thyTreg 5.000.000 |
| Phase A: standard of care | No intervention | –Standard of care |
| Phase B: 10.000.000 thyTreg /kg | Experimental | Biological: Allogeneic thyTreg 10.000.000Allogeneic thyTreg 10.000.000 |
| Phase B: standard of care | No intervention | –Standard of care |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient over 18 to 65 years of age
- Patient Informed and non-opposed to the research by his medical doctor during hospitalization
- Patient with clinical, radiological, gasometric and immunological criteria defined as:
Key exclusion criteria (17 listed)
- Pregnancy or breast feeding
- Body mass index >35
- Patients not expected to survive 48 hours after enrolment based on clinical assessment
- Patients with an extracorporeal respiratory support
- Neutropenia (absolute neutrophil count <1000/uL)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogeneic thyTreg 5.000.000Also: Allogeneic thyTreg cellsTreg lymphocytic cells, differentiated, allogeneic, of thymic tissue, expanded and stimulated with Interleukin (IL-) 2 (thyTreg) | Biological | Phase A: 5.000.000 thyTreg /kg |
| Allogeneic thyTreg 10.000.000Also: Allogeneic thyTreg cellsTreg lymphocytic cells, differentiated, allogeneic, of thymic tissue, expanded and stimulated with Interleukin (IL-) 2 (thyTreg) | Biological | Phase B: 10.000.000 thyTreg /kg |
Primary outcome
1. Incidence of infusion-related adverse events (safety) by type, frequency, severity, and causality
Time frame: 24 months
16 secondary outcomes
Length of intensive care unit stay
Time frame: 24 months
Oxygenation improvement as assessed using PaO2/FiO2 and/or SaO2/FiO2
Time frame: 24 months
Change in clinical status as assessed using Sequential Organ Failure Assessment Score
Time frame: 24 months
Change in clinical status as assessed using Acute Physiology and Chronic Health disease Classification System (APACHE) III
Time frame: 24 months
Change in clinical status as assessed using Barthel score
Time frame: 24 months
Change in myocardial function as measured by mitral and tricuspid regurgitation using doppler echocardiography
Time frame: 24 months
Change in myocardial function as measured by mitral and tissue mitral doppler using doppler echocardiography
Time frame: 24 months
Change in myocardial function as measured by tricuspid and tissue tricuspid using doppler echocardiography
Time frame: 24 months
Change in SARS-CoV-2 positivity or etiology of ARDS assessed using diagnostics test
Time frame: 24 months
Change From Baseline in ferritin parameter
Time frame: 24 months
Change From Baseline in interleukin 6 (IL-6)
Time frame: 24 months
Change From Baseline in C-Reactive Protein (PCR)
Time frame: 24 months
Change From Baseline in Treg cells number in peripheral blood
Time frame: 24 months
Number of T cells, B cells, NK cells, monocytes, dendritic cells, and granulocytes in peripheral blood
Time frame: 24 months
Change From Baseline in cytokines levels of interferon gamma, tumor necrosis factor alpha and interleukins (IL-6 and IL-10).
Time frame: 24 months
Overall patient survival rate at 24 months
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rafael Correa-Rocha, PhD principal investigator
Hospital General Universitario Gregorio Marañon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Allogeneic thyTreg 5.000.000 and Allogeneic thyTreg 10.000.000 in people with Systemic Inflammatory Response Syndrome, run by Hospital General Universitario Gregorio Marañon at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marta Martínez-Bonet, PhD (34 915866455, marta.mbonet@iisgm.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1. Incidence of infusion-related adverse events (safety) by type, frequency, severity, and causality (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.